Takeda resubmits alogliptin and fixed-dose combination therapy NDA to FDA

Takeda Pharmaceutical Company Limited (Takeda) announced today that Takeda Global Research & Development Center, Inc., resubmitted two New Drug Applications (NDA) to the United States (U.S.) Food and Drug Administration (FDA) for alogliptin and the fixed-dose combination therapy alogliptin/pioglitazone, which combines alogliptin with pioglitazone in a single tablet. The FDA will review the NDA resubmissions within the next six months. Pioglitazone was approved in 1999 for the treatment of type 2 diabetes as an adjunct to diet and exercise. Alogliptin is a selective dipeptidyl peptidase IV inhibitor (DPP-4i) under investigation in the U.S. for the treatment of type 2 diabetes as an adjunct to diet and exercise. Discovered by Takeda San Diego, Inc., alogliptin is designed to slow the inactivation of incretin hormones GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic peptide), which play a role in regulating blood glucose levels.

"We believe interim results from a cardiovascular outcomes trial satisfy the FDA's cardiovascular safety requirements to allow the Agency to complete its review of our NDA, and further support the product profile of alogliptin," said David Recker, M.D., senior vice president, clinical science, Takeda Global Research & Development Center. "If approved, alogliptin/pioglitazone will be the first type 2 diabetes treatment option in the U.S. to include both a DPP-4 inhibitor and a thiazolidinedione in a single tablet."

The NDA resubmissions include interim results from the EXAMINE (EXamination of CArdiovascular OutcoMes: AlogliptIN vs. Standard of CarE in Patients with Type 2 Diabetes Mellitus and Acute Coronary Syndrome) study, a cardiovascular outcomes trial requested by the FDA to satisfy the criteria outlined in the December 2008 "Guidance for Industry: Diabetes Mellitus -- Evaluating Cardiovascular Risk in New Antidiabetic Therapies to Treat Type 2 Diabetes." The EXAMINE study was designed to comply with the Guidance. This randomized, double-blind, placebo-controlled outcomes study continues to evaluate cardiovascular endpoints following treatment with alogliptin in addition to standard of care, versus standard of care alone, in patients with type 2 diabetes and a recent acute coronary syndrome (ACS). Final study results are expected in 2014.

"The NDA resubmissions mark a significant milestone for Takeda in the U.S., underscoring our deeply held commitment to providing therapeutic options for patients living with type 2 diabetes," said Robert Spanheimer, M.D., vice president, medical and scientific affairs, Takeda Pharmaceuticals North America. "We are confident in the data available for alogliptin, and look forward to building upon our global expertise in the diabetes therapeutic area."